ArticleThe Journal of clinical investigation2015
Pharmacological HIF2α inhibition improves VHL disease-associated phenotypes in zebrafish model.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Familial Kidney Cancer: Implications of New Syndromes and Molecular Insights.European urology · 2019Pooled it
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- Hypoxia-mediated epicardial signaling coordinates coronary angiogenesis and myocardial expansion during zebrafish ventricle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Macrophage adaptation to hypoxia in the tuberculous granuloma potentiates mycobacterium-induced mitochondrial damage and granuloma necrosis.bioRxiv : the preprint server for biology · 2026Article
- miR-34a is a tumor suppressor in zebrafish and its expression levels impact metabolism, hematopoiesis and DNA damage.PLoS genetics · 2024Article
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- A versatile, automated and high-throughput drug screening platform for zebrafish embryos.Biology open · 2021Article
- Tpr Deficiency Disrupts Erythroid Maturation With Impaired Chromatin Condensation in Zebrafish Embryogenesis.Frontiers in cell and developmental biology · 2021Article
- Article
- Von Hippel-Lindau Disease: Current Challenges and Future Prospects.OncoTargets and therapy · 2020Review
- Algorithmic assessment of missense mutation severity in the Von-Hippel Lindau protein.PloS one · 2020Article
- Repurposing propranolol as an antitumor agent in von Hippel-Lindau disease.Journal of neurosurgery · 2019Article
- Metabolomics and Age-Related Macular Degeneration.Metabolites · 2018Review
- Translational repression of HIF2α expression in mice with Chuvash polycythemia reverses polycythemia.The Journal of clinical investigation · 2018Article
- Hif-1α regulates macrophage-endothelial interactions during blood vessel development in zebrafish.Nature communications · 2017Article
- Discovery of a murine model of clinical PAH: Mission impossible?Trends in cardiovascular medicine · 2017Review
- Loss of vhl in the zebrafish pronephros recapitulates early stages of human clear cell renal cell carcinoma.Disease models & mechanisms · 2016Article
- The Endothelial Prolyl-4-Hydroxylase Domain 2/Hypoxia-Inducible Factor 2 Axis Regulates Pulmonary Artery Pressure in Mice.Molecular and cellular biology · 2016Article
- Article
- Zebrafish Models of Prader-Willi Syndrome: Fast Track to Pharmacotherapeutics.Diseases (Basel, Switzerland) · 2016Article
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
Patients with a germline mutation in von Hippel-Lindau (VHL) develop renal cell cancers and hypervascular tumors of the brain, adrenal glands, and pancreas as well as erythrocytosis. These phenotypes are driven by aberrant expression of HIF2α, which induces expression of genes involved in cell proliferation, angiogenesis, and red blood cell production. Currently, there are no effective treatments available for VHL disease. Here, using an animal model of VHL, we report a marked improvement of VHL-associated phenotypes following treatment with HIF2α inhibitors. Inactivation of vhl in zebrafish led to constitutive activation of HIF2α orthologs and modeled several aspects of the human disease, including erythrocytosis, pathologic angiogenesis in the brain and retina, and aberrant kidney and liver proliferation. Treatment of vhl(-/-) mutant embryos with HIF2α-specific inhibitors downregulated Hif target gene expression in a dose-dependent manner, improved abnormal hematopoiesis, and substantially suppressed erythrocytosis and angiogenic sprouting. Moreover, pharmacologic inhibition of HIF2α reversed the compromised cardiac contractility of vhl(-/-) embryos and partially rescued early lethality. This study demonstrates that small-molecule targeting of HIF2α improves VHL-related phenotypes in a vertebrate animal model and supports further exploration of this strategy for treating VHL disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.